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6.6.2 Bisphosphonates

First line drugs Second line drugs Specialist drugs Secondary care drugs

Notes:

  • Oral bisphosphonates are absorbed very poorly; therefore counselling should be given to the patient as to how and when administration is most appropriate. 
  • All oral bisphosphonate should be taken in combination with calcium & vitamin D. Both Adcal D3®, Calcichew® D3 Forte and Calceos® are the choices in the formulary (see Chapter 9), the patient should be offered the product they like the best to achieve concordance.
  • Prescribers are reminded to check that an annual infusion of zoledronic acid has not been given, prior to commencing oral bisphosphonates.

MHRA Drug Safety Update November 2009:

  • The risk of developing osteonecrosis of the jaw (ONJ) with oral bisphosphonates seems to be low. The risk of ONJ is substantially greater for patients receiving I/V bisphosphonates for cancer indications than for patients receiving oral bisphosphonates for oseteoporosis of Paget's disease
  • To minimise risk all patients should have a dental check-up before bisphosphonate treatment. All other patients who start bisphosphonates should have a dental examination only if they have poor dental status
  • During treatment, patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling.

MHRA Drug Safety Update June 2011:

  • Atypical femoral fractures have been reported rarely with bisphosphonate therapy, mainly in patients receiving long-term treatment for osteoporosis. They are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture
  • Discontinuation of therapy in patients suspected to have an atypical femur fracture should be considered while they are evaluated, and should be based on an assessment of the benefits and risks of treatment for the individual
  • During treatment, patients should be advised to report any thigh, hip, or groin pain. Any patient who presents with such symptoms should be evaluated for an incomplete femur fracture
  • The optimum duration of treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of bisphosphonate therapy for individual patients, particularly after 5 or more years of use

Alendronic acid

  • Tablets 10mg, 70mg

Notes:

  • Alendronic acid 70mg is a ‘special container' pack of four tablets. These should not be prescribed on weekly prescriptions as the pack can not be split by the pharmacy to provide one tablet.
  • Alendronic acid, and possibly risedronate, can cause severe oesophageal reactions. Patients should be advised to discontinue treatment and seek medical attention if they develop symptoms of oesophageal irritation, new or worsening heartburn, pain on swallowing or retrosternal pain. Strict guidelines on administration should be followed.

Disodium Etidronate

  • Tablets 200mg

Risedronate

  • Tablets 5mg, 30mg, 35mg

Ibandronic Acid

  • Injection 1mg/ml

Sodium Clodronate

  • Tablets 800mg

Zoledronic Acid

  • Zometa concentrate for IV infusion 800 micrograms/ml, 5ml (4mg) vial
  • Aclasta I/V infusion 50 micrograms/ml 100ml bottle

Denosumab

Denosumab

  • Subcutaneous injection, prefilled syringe 60mg per ml
  • Injection 70mg per ml 1.7ml (120mg) vial

To be used in line with:

MHRA Drug Safety Update Feb 2013 vol 6, issue 7: A1. Atypical femoral fractures have been reported rarely in patients with postmenopausal osteoporosis receiving long-term (≥2.5 years) treatment with denosumab 60mg in a clinical trial.
During denosumab treatment, patients presenting with new or unusual thigh, hip or groin pain should be evaluated for an incomplete femoral fracture. Discontinuation of denosumab therapy should be considered if an atypical femur fracture is suspected, while the patient is evaluated.

MHRA Drug Safety Update Oct 2012 vol 6, issue 3: A3. The following precautions should be followed to minimise the risk of hypocalcaemia with denosumab:
Contraindications:

  • Denosumab 120mg (for cancer indications) should not be used in patients with severe, untreated hypocalcaemia
  • Denosumab 60mg (for osteoporosis indications) should not be used in patients with hypocalcaemia, regardless of severity (the contraindications vary between the two doses, because their indications are different).

Warnings and recommendations:

  • Pre-existing hypocalcaemia must be corrected prior to initiating denosumab, and supplementation of calcium and vitamin D is required in all patients receiving 120mg denosumab unless hypercalcaemia is present.
  • Adequate intake of calcium and vitamin D is important in all patients receiving 60mg denosumab
  • Patients with severe renal impairment (creatinine clearance <30 mL; eGFR 15 – 29 mL/min/1.73m2) or receiving dialysis are at greater risk of developing hypocalcaemia, and monitoring of calcium levels in these patients is recommended.

Strontium ranelate       

Strontium

  • Granules 2g       

MHRA Drug Safety Update (June 2011): Strontium is known to increase the risk of venous thromboembolic events (VTE) and should not be used in patients with current or previous VTE, including deep vein thrombosis and pulmonary embolism, or in patients with temporary or permanent immobilisation (eg post-surgical recovery or prolonged bed rest). The need for continued treatment with strontium ranelate should also be re-evaluated in patients over 80 years who have been diagnosed at risk of VTE, as the risk of VTE in this group may be increased

Strontium ranelate is also associated with serious skin and hypersensitivity reactions such as drug rash with eosinophilia and systemic symptoms (DRESS). Although the risk is low, prescribers are advised to be alert to signs and symptoms of serious skin reactions with strontium ranelate. The likely time-to-onset of such events is the first few weeks of treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis and usually within 3 – 6 weeks for DRESS. Early diagnosis and discontinuation of treatment produce the best results, and patients should be advised accordingly

Please refer to:

Guidelines for the treatment and prevention of osteoporosis

  1. Fracture risk should be assessed in postmenopausal women and in men aged 50 years or more with the risk factors outlined where assessment would influence management.
  2. Women with a prior fragility fracture should be considered for treatment without the need for further risk assessment although BMD measurement may sometimes be appropriate, particularly in younger postmenopausal women.
  3. In the presence of other clinical risk factors, the ten year probability of a major osteoporotic fracture (clinical spine, hip, forearm or humerus) should be determined using FRAX® (www.shef.ac.uk/FRAX). Men and women with probabilities below the lower assessment threshold can be reassured. Those with probabilities above the lower assessment threshold but below the upper assessment threshold can be considered for testing with BMD using DXA and their fracture probability reassessed. Men and women with probabilities above the intervention threshold should be considered for treatment.
  4. In men and women who require a BMD test, fracture probabilities should be recomputed with FRAX®. Treatment can be considered in those in whom fracture probabilities lie above the intervention threshold.
  5. Osteoporosis management aims to reduce the risk of future fracture not to increase bone mineral density (BMD) and any decision on treatment must reflect this.
  6. Drug treatment of osteoporosis is only one part of any strategy to reduce the burden of disease and financial impact of fragility fractures in the population. Any strategy to prevent fractures should include falls prevention measures, population wide interventions to reduce osteoporosis as well as measures to reduce the impact if falls do occur.
  7. Early treatment does not improve long-term outcomes. Decrease in risk of fracture declines to pre-treatment levels after 5 years.
  8. The gold standard for monitoring BMD is DEXA of hip and spine. There is no role for forearm or heel scanning in the diagnosis of osteoporosis in targeting therapy to reduce fracture risk.  In most cases a diagnosis of osteoporosis will be based on T-score assessment alone. In non-Caucasians, males and younger patients consideration of Z-score may be necessary to confirm diagnosis of osteoporosis.
  9. Before referring any patients for DEXA scan consider:
    • BMD is a poor predictor of those who will have a fracture. There is no evidence to support mass screening of BMD in the older population. The emphasis should be on identifying high-risk patients through selective case finding. There is little value investigating BMD in patients over 75 years old, other risk assessment tools that do not involve BMD may be useful. Patients under 65 have a very low risk of fracture and should only be investigated if there are significant and compelling risk factors.
    • Patients should only be referred for BMD if the result is likely to alter management.
    • Osteoporosis can be diagnosed in patients with radiological evidence of vertebral fracture without need for BMD scan.
    • Follow-up scans are not routinely required for patients continuing on anti-resorptive treatment. Fracture risk reduction occurs within 6 months of starting treatment and is disproportionate to any change in BMD.

Intravenous infusion

Disodium pamidronate

  • Injection 15mg, 30mg, 60mg, 90mg          

Notes:

  • IV disodium pamidronate is licensed to treat hypercalcaemia, osteolytic lesions and bone pain linked to bone/skeletal metastases and that related to Paget’s disease.
  • Disodium pamidronate may be used in the treatment of osteoporosis (unlicensed). The required dose is diluted in 0.9% sodium chloride to a concentration of not more than 60mg in 250ml and given at a rate not exceeding 1mg per minute.

Return to Chapter: 6. Endocrine System

Last updated by: Carol Webb on 02-05-2013 09:28